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Efficacy and Safety of Cetuximab in Metastatic Penile Carcinoma (PENILANE) (PENILANE)

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ClinicalTrials.gov Identifier: NCT02014831
Recruitment Status : Withdrawn (Industry decline to supply study drug)
First Posted : December 18, 2013
Last Update Posted : February 25, 2016
Sponsor:
Information provided by (Responsible Party):
Centre Leon Berard

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of Cetuximab in metastatic penile carcinoma

Condition or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Penis Drug: Cetuximab Drug: TIP Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study to Evaluate the Efficacy and Safety of Cetuximab in Metastatic Penile Carcinoma
Study Start Date : February 2016
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Active Comparator: TIP
"Reference" arm; Patients will be treated with 6 cycles of Paclitaxel + Ifosfamide + Cisplatin (TIP treatment)
Drug: TIP

The TIP combination of treatments will be administered on specific days within a 21-days-cycle and for a maximum of 6 cycles as follow :

PACLITAXEL I.V infusion of 175 mg/m2, for 3 hours, on Day 1 of the cycle.

IFOSFAMIDE I.V infusion of 1200 mg/m2, for 2 hours, on Day 1, Day 2, Day 3 of the cycle.

CISPLATINE I.V infusion of 25 mg/m2, for 1 hour, on Day 1, Day 2, Day 3.

In case of documented toxicities, 2 drugs doses reductions are allowed according specific algorithms indicated in protocol


Experimental: Cetuximab + TIP
"Experimental" arm: Patients will be treated with 6 cycles of Paclitaxel + Ifosfamide + Cisplatin (TIP treatment) and weekly infusion of Cetuximab.
Drug: Cetuximab

Cetuximab treatment will be administered on specific days within a 21-days-cycle and for a maximum of 6 cycles as follow :

CETUXIMAB I.V infusion of 400 mg/m2 on cycle 1 Day 0 for 2 hours, then 250 mg/m2 for subsequent infusions for 1 hour on Day 8, Day 15 and next cycles Day1, Day8, Day15.

In case of documented toxicities, 2 drugs doses reductions are allowed according specific algorithms indicated in protocol


Drug: TIP

The TIP combination of treatments will be administered on specific days within a 21-days-cycle and for a maximum of 6 cycles as follow :

PACLITAXEL I.V infusion of 175 mg/m2, for 3 hours, on Day 1 of the cycle.

IFOSFAMIDE I.V infusion of 1200 mg/m2, for 2 hours, on Day 1, Day 2, Day 3 of the cycle.

CISPLATINE I.V infusion of 25 mg/m2, for 1 hour, on Day 1, Day 2, Day 3.

In case of documented toxicities, 2 drugs doses reductions are allowed according specific algorithms indicated in protocol





Primary Outcome Measures :
  1. Evaluation of the antitumor activity of Cetuximab treatment in terms of Objective Response Rate (ORR) at the end of treatment [ Time Frame: 4 weeks after the day 1 of the last cycle administered (i.e between 4 weeks to 20 weeks after randomization, according to the amount of administered cycles) ]

    Patients will be treated by TIP +/- Cetuximab for 1 cycle of 21 days. Subsequent treatment cycles will be performed only if patients meet correct biological analyses as defined by protocol, with a maximum of 5 more cycles of 21 days. Thus, the treatment duration will vary between patients from 3 weeks to 18 weeks. The treatment efficacy will be evaluated 28 days after the day 1 of the last cycle administered. Thus ORR will be evaluated between 4 weeks to 20 weeks after randomization, according to the amount of administered cycles.

    ORR is defined as the proportion of patients with best response consisting in a Complete Response (CR) or a Partial Response (PR) from the date of randomization to the date of the end of treatment visit (i.e 6 cycles of treatment as maximum) evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1



Secondary Outcome Measures :
  1. Evaluation of the Safety Profile of Cetuximab treatment [ Time Frame: From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion ]
    Safety profile is assessed throughout the study by incidence and intensity of Adverse Events displayed by patients using the CTCAE version 4.0

  2. Evaluation of the antitumor activity of Cetuximab treatment in terms of Overall Survival (OS) at the end of the study [ Time Frame: From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion ]
    OS is defined as the time from the date of randomization to the date of death due to any cause. If a patient is not known to have died at the time of the analysis, OS will be censored at the date of last contact.

  3. Evaluation of the antitumor activity of Cetuximab treatment in terms of Progression-Free Survival (PFS) at the end of the study [ Time Frame: From patient randomization up to the end of study i.e 28 months maximum after first patient inclusion ]
    PFS is defined as the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event at the time of the analysis, PFS will be censored at the date of last adequate tumor assessment.

  4. Evaluation of Quality of Life during the Cetuximab treatment [ Time Frame: From patient randomization up to the end of treatment (i.e between 4 weeks to 20 weeks after randomization, according to the amount of administered cycles) ]
    Quality of life is assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30. It will be evaluated at Screening, at the beginning of cycle 4, and at the end of treatment i.e after 6 cycles maximum



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA :

  • Male older than 18 years-old,
  • Squamous cell carcinoma of the penis of clinical stages N3 and/or M1,
  • Central Histological confirmation of diagnosis of wild-type K-ras penis cancer (histological documentation of the mutational status prior to each patient's registration).

Nota Bene: an archival tumor sample must be available.

  • At least one measurable lesion according to the RECIST version 1.1. In case of relapsing patient, documented progression as per RECIST version 1.1,
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2,
  • Life expectancy ≥ 6 months,
  • Adequate organs functions defined as the following (transfusion is not allowed within 7 days prior to lab test performed to assess the eligibility):

    • Hemoglobin ≥ 9 mg/dL,
    • Absolute Neutrophils Count ≥ 1,5 Gi/l,
    • Platelets ≥ 100 Gi/l,
    • Creatinine ≤ 1,5 x Upper Limit of Normal (ULN) and Creatinine clearance ≥ 60 ml/min (calculated with Cockcroft formula or Modification of Diet in Renal Disease (MDRD) formula for patients older than 65 years old)
    • Aspartate aminotransferase (ASAT) and Alanine aminotransferase (ALAT) ≤ 2,5 x ULN (≤ 5 x ULN in presence of liver metastasis)
    • Total bilirubin ≤ 1,5 x ULN,
  • Willingness to use effective contraceptive method during the whole treatment period and up to 4 months after the last study drug administration,
  • Affiliated to the French social security system,
  • Subjects must provide written informed consent prior to perform any study-specific procedures or assessments and must be willing to comply with treatment and follow up.

EXCLUSION CRITERIA :

  • Symptomatic metastases of Central nervous system (CNS) requiring or having required steroids or enzyme-inducing anticonvulsants within 4 weeks before inclusion,
  • Previous treatment with paclitaxel, or ifosfamide, or cetuximab, or any monoclonal antibody, and or any drug targeting EGF Receptor,
  • Local and/or resectable disease,
  • Prior history of other malignancies other than penis cancer (except for basal cell or squamous cell carcinoma of the skin and superficial bladder carcinoma) unless the subject has been free of the disease for at least 3 years,
  • No resolution of specific toxicities related to any prior anti-cancer therapy to Grade ≤1 according to the CTCAE v.4.0 (except lymphopenia and alopecia),
  • Active peripheral or motor neuropathy of any CTCAE grade and due to any cause,
  • Known hypersensitivity or allergy or contraindication to at least one of the study drugs
  • In case of previous chemotherapy, wash out period of less than 5 half-lives of treatment before study entry,
  • Clinically significant cardiovascular disease including:

    • Myocardial infarction within 3 months,
    • Congestive heart failure of the New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening Left Ventricular Ejection Fraction (LVEF) assessment ≥ 45%,
    • Prolonged QT interval defined as screening corrected QT interval (QTc) > 470 ms (Fridericia correction formula),
    • History of clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, ...),
    • History of Mobitz II 2nd degree or 3rd degree heart block without a permanent pacemaker in place,
    • Hypotension (systolic BP < 86 mmHg) or bradycardia with a heart rate < 50 bpm,
    • Uncontrolled hypertension as indicated by a resting systolic BP > 170 mmHg or diastolic BP > 105 mmHg despite an optimal treatment,
  • Major surgery or radiation therapy within 4 weeks prior first study drug administration or already planned during the study,
  • Any pulmonary, thyroid, renal, hepatic severe/uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol,
  • Active uncontrolled viral, fungal or bacterial infection,
  • Patient who cannot abstain from vaccine against yellow fever, prophylactic use of phenytoin or derivate, or any drug which can strongly interfere with the sub-units 2C8 and/or 3A4 of the cytochrome P450 (Cf. appendix 5) Nota Bene: in case of poor interference with these sub-units, treatments with a narrow therapeutic index should be avoided.
  • Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements (participants must agree to refrain from substance abuse use during the entire course of the study),
  • Concomitant participation to another clinical trial with active agent during the study (concomitant non interventional study will be allowed).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02014831


Locations
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France
CHRU Strasbourg
Strasbourg, Bas Rhin, France, 67098
Institut Paoli Calmettes
Marseille, Bouches du Rhône, France, 13273
Institut Bergonié
Bordeaux, Gironde, France, 33076
Institut Claudius Regaud
Toulouse, Haute Garonne, France, 31052
Institut Curie
Paris, Ile de France, France, 75005
APHP Hôpital Saint Louis
Paris, Ile de France, France, 75475
Centre Léon Bérard
Lyon, Rhône, France, 69373
Sponsors and Collaborators
Centre Leon Berard
Investigators
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Principal Investigator: Helen BOYLE, Doctor Centre Leon Berard

Publications:
Curado M.P., Edwards B., Shin H.R. et al. Cancer Incidence in Five continents. Sci Publ. 2007. 160:570-573.
Dorff T. EGFR, TS and ERCC1 expression in penile squamous cancer. ASCO GU 2011. Not yet published.
Valverde C.M. BRAF and KRAS mutations in penile cancer and their correlation with clinical features. ASCO GU 2011. Not yet published.

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Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT02014831     History of Changes
Other Study ID Numbers: PENILANE
First Posted: December 18, 2013    Key Record Dates
Last Update Posted: February 25, 2016
Last Verified: February 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Centre Leon Berard:
Squamous Cell Carcinoma of the penis
Stage N3
Metastasis
TIP
Cetuximab
Objective Response Rate
Safety profile
Overall Survival
Progression Free Survival
Quality of Life

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Penile Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Penile Diseases
Paclitaxel
Cetuximab
Ifosfamide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents, Alkylating
Alkylating Agents